Functional and effective frontotemporal connectivity and genetic risk for schizophrenia

Georg Winterer, Richard Coppola, Michael F. Egan, Terry E. Goldberg, Daniel Weinberger

Research output: Contribution to journalArticle

Abstract

Background: Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal connectivity are trait markers of genetic risk for schizophrenia. Methods: We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings, and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG) evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of functional connectivity); and 2) we performed structural equation modeling of the effective connectivity between the frontal P300 and temporoparietal P300-amplitude. Results: Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence. At peak activation during the P300 time-window, a negative ("inhibitory") frontotemporal path coefficient was found in normal controls, whereas a positive coefficient was seen in schizophrenic patients with siblings being intermediate. Intra-class correlations between sib-pairs and relative risk estimates of the applied connectivity measures were non-significant. Topographic correlation matrix analyses suggested that the altered functional and effective frontotemporal connectivity indirectly reflect regional abnormalities of increased activation variance. Conclusions: Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically determined abnormalities of frontal and temporoparietal microcircuits. The reasons why frontotemporal connectivity appears to be a poor predictor of genetic risk for schizophrenia are discussed.

Original languageEnglish (US)
Pages (from-to)1181-1192
Number of pages12
JournalBiological Psychiatry
Volume54
Issue number11
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

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Schizophrenia
Siblings
Electroencephalography
Functional Neuroimaging
Genetic Markers
Evoked Potentials

Keywords

  • Frontotemporal connectivity
  • Genetics
  • P300
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Functional and effective frontotemporal connectivity and genetic risk for schizophrenia. / Winterer, Georg; Coppola, Richard; Egan, Michael F.; Goldberg, Terry E.; Weinberger, Daniel.

In: Biological Psychiatry, Vol. 54, No. 11, 01.12.2003, p. 1181-1192.

Research output: Contribution to journalArticle

Winterer, Georg ; Coppola, Richard ; Egan, Michael F. ; Goldberg, Terry E. ; Weinberger, Daniel. / Functional and effective frontotemporal connectivity and genetic risk for schizophrenia. In: Biological Psychiatry. 2003 ; Vol. 54, No. 11. pp. 1181-1192.
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